Mitochondria: Pharmacological manipulation of cell death

Journal of Clinical Investigation

Volumn 115, Issue 10, 2005, Pages 2640-2647

  Bouchier Hayes, Lisa ^a   Lartigue, Lydia ^a   Newmeyer, Donald D ^a  

^a LA JOLLA INSTITUTE FOR ALLERGY AND IMMUNOLOGY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 ETHYL 2 [[3 ETHYL 5 (3 METHYLBENZOTHIAZOLIN 2 YLIDENE) 4 OXOTHIAZOLIDIN 2 YLIDENE]METHYL]PYRIDINIUM CHLORIDE; 2 AMINO 6 BROMO 4 (1 CYANO 2 ETHOXY 2 OXOETHYL) 4H CHROMENE 3 CARBOXYLIC ACID ETHYL ESTER; 4 [4 (4' CHLORO 2 BIPHENYLYLMETHYL) 1 PIPERAZINYL] N [4 [3 DIMETHYLAMINO 1 (PHENYLTHIOMETHYL)PROPYLAMINO] 3 NITROBENZENESULFONYL]BENZAMIDE; 4 [N (S GLUTATHIONYLACETYL)AMINO]PHENYLARSENOXIDE; 6 [3 (1 ADAMANTYL) 4 HYDROXYPHENYL] 2 NAPHTHOIC ACID; ANTIMYCIN A1; ANTINEOPLASTIC AGENT; ANTIOXIDANT; ARSENIC TRIOXIDE; ARSENOSOBENZENE; ASCORBIC ACID; BENZOPYRAN DERIVATIVE; BETULIC ACID; BH31S; BORTEZOMIB; CHALCONE DERIVATIVE; CISPLATIN; CYTARABINE; DIAZEPAM; DOXORUBICIN; ETOPOSIDE; F 16; FLUOROURACIL; LONIDAMINE; MT 21; N SEC BUTYL 1 (2 CHLOROPHENYL) N METHYL 3 ISOQUINOLINECARBOXAMIDE; NORPHENAZONE; PACLITAXEL; PHOTOSENSITIZING AGENT; PHTHALOCYANINE DERIVATIVE; PKF 1195; PORPHYRIN DERIVATIVE; RHODAMINE 123; RO5 4864; S 14; S 15; S 17; THIOL DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VINCRISTINE; YC 137;

ACUTE GRANULOCYTIC LEUKEMIA; AMINO ACID SEQUENCE; APOPTOSIS; BREAST CANCER; CANCER; CELL DEATH; CELL PERMEABILIZATION; CHRONIC LYMPHATIC LEUKEMIA; CLINICAL TRIAL; DRUG EFFECT; DRUG EFFICACY; DRUG INDICATION; DRUG MECHANISM; ENDOMETRIUM CARCINOMA; ENZYME RELEASE; GASTROINTESTINAL CARCINOMA; HUMAN; LEUKEMIA; LUNG NON SMALL CELL CANCER; LYMPHOMA; MITOCHONDRIAL MEMBRANE; MULTIPLE MYELOMA; NONHUMAN; OVARY CANCER; PHOTODYNAMIC THERAPY; PRIORITY JOURNAL; PROMYELOCYTIC LEUKEMIA; PROTEIN FUNCTION; PROTEIN LOCALIZATION; REVIEW; SEQUENCE HOMOLOGY; TUMOR CELL;

ANIMALS; APOPTOSIS; CELL MEMBRANE PERMEABILITY; DRUG DESIGN; HUMANS; MITOCHONDRIA; PHARMACEUTICAL PREPARATIONS; SIGNAL TRANSDUCTION;

EID: 26444468146     PISSN: 00219738     EISSN: None     Source Type: Journal    
DOI: 10.1172/JCI26274     Document Type: Review

References (118)

1. Weissig, V., Boddapati, S.V., D'Souza, G.G.M., and Cheng, S.M. 2004. Targeting of low-molecular weight drugs to mammalian mitochondria. Drug Design Reviews - Online. 1:15-28.
2. Martin, S.J., and Green, D.R. 1995. Protease activation during apoptosis: death by a thousand cuts? Cell. 82:349-352.
3. Newmeyer, D.D., and Ferguson-Miller, S. 2003. Mitochondria: releasing power for life and unleashing the machineries of death. Cell. 112:481-490.
4. Adrain, C., and Martin, S.J. 2001. The mitochondrial apoptosome: a killer unleashed by the cytochrome seas. Trends Biochem. Sci. 26:390-397.
5. Du, C., Fang, M., Li, Y., Li, L., and Wang, X. 2000. Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition. Cell. 102:33-42.
6. Suzuki, Y., et al. 2001. A serine protease, HtrA2, is released from the mitochondria and interacts with XIAP, inducing cell death. Mol. Cell. 8:613-621.
7. Klein, J.A., et al. 2002. The harlequin mouse mutation downregulates apoptosis-inducing factor. Nature. 419:367-374.
8. Jones, J.M., et al. 2003. Loss of Omi mitochondrial protease activity causes the neuromuscular disorder of mnd2 mutant mice. Nature. 425:721-727.
9. Uren, R.T., et al. 2005. Mitochondrial release of pro-apoptotic proteins: electrostatic interactions can hold cytochrome c but not Smac/DIABLO to mitochondrial membranes. J. Biol. Chem. 280:2266-2274.
10. Otera, H., Ohsakaya, S., Nagaura, Z.I., Ishihara, N., and Mihara, K. 2005. Export of mitochondrial AIF in response to proapoptotic stimuli depends on processing at the intermembrane space. EMBO J. 24:1375-1386.
11. Polster, B.M., Basanez, G., Etxebarria, A., Hardwick, J.M., and Nicholls, D.G. 2005. Calpain I induces cleavage and release of apoptosis-inducing factor from isolated mitochondria. J. Biol. Chem. 280:6447-6454.
12. Von Ahsen, O., Waterhouse, N.J., Kuwana, T., Newmeyer, D.D., and Green, D.R. 2000. The 'harmless' release of cytochrome c. Cell Death Differ. 7:1192-1199.
13. Kuwana, T., and Newmeyer, D.D. 2003. Bcl-2-family proteins and the role of mitochondria in apoptosis. Curr. Opin. Cell Biol. 15:691-699.
14. Tsujimoto, Y., and Shimizu, S. 2000. VDAC regulation by the Bcl-2 family of proteins. Cell Death Differ. 7:1174-1181.
15. Korsmeyer, S.J., et al. 2000. Pro-apoptotic cascade activates BID, which oligomerizes BAK or BAX into pores that result in the release of cytochrome c. Cell Death Differ. 7:1166-1173.
16. Harris, M.H., and Thompson, C.B. 2000. The role of the Bcl-2 family in the regulation of outer mitochondrial membrane permeability. Cell Death Differ. 7:1182-1191.
17. Martinou, J.C., and Green, D.R. 2001. Breaking the mitochondrial barrier. Nat. Rev. Mol. Cell Biol. 2:63-67.
18. Zamzami, N., and Kroemer, G. 2001. The mitochondrion in apoptosis: how Pandora's box opens [review]. Nat. Rev. Mol. Cell Biol. 2:67-71.
19. Martinou, J.C., Desagher, S., and Antonsson, B. 2000. Cytochrome c release from mitochondria: all or nothing. Nat. Cell Biol. 2:E41-E43.
20. Kuwana, T., et al. 2002. Bid, Bax, and lipids cooperate to form supramolecular openings in the outer mitochondrial membrane. Cell. 111:331-342.
21. Scorrano, L., et al. 2002. A distinct pathway remodels mitochondrial cristae and mobilizes cytochrome c during apoptosis. Dev. Cell. 2:55-67.
22. Bossy-Wetzel, E., Barsoum, M.J., Godzik, A., Schwarzenbacher, R., and Lipton, S.A. 2003. Mitochondrial fission in apoptosis, neurodegeneration and aging. Curr. Opin. Cell Biol. 15:706-716.
23. Scorrano, L. 2003. Divide et impera: Ca2+ signals, mitochondrial fission andsensitization to apoptosis. Cell Death Differ. 10:1287-1289.
24. Lee, Y., Jeong, S.-Y., Karbowski, M., Smith, C.L., and Youle, R.J. 2004. Roles of the mammalian mitochondrial fission and fusion mediators Fis1, Drp1, and Opa1 in apoptosis. Mol. Biol. Cell. 15:5001-5011.
25. Kokoszka J.E., et al. 2004. The ADP/ATP translocator is not essential for the mitochondrial permeability transition pore. Nature. 427:461-465.
26. Halestrap, A.P. 2004. Mitochondrial permeability: dual role for the ADP/ATP translocator? Nature. 430:1 page following 983.
27. Ichas, F., and Mazat, J.P. 1998. From calcium signaling to cell death: two conformations for the mitochondrial permeability transition pore. Switching from low- to high-conductance state. Biochim. Biophys. Acta. 1366:33-50.
28. Crompton, M. 1999. The mitochondrial permeability transition pore and its role in cell death. Biochem. J. 341:233-249.
29. Jurgensmeier, J.M., et al. 1998. Bax directly induces release of cytochrome c from isolated mitochondria. Proc. Natl. Acad. Sci. U. S. A. 95:4997-5002.
30. De Giorgi, P., et al. 2002. The permeability transition pore signals apoptosis by directing Bax translocation and multimerization. FASEB J. 16:607-609.
31. Bossy-Wetzel, E., Newmeyer, D.D., and Green, D.R. 1998. Mitochondrial cytochrome C release in apoptosis occurs upstream of DEVD-specific caspase activation and independently of mitochondrial transmembrane depolarization. EMBO J. 17:37-49.
32. von Ahsen, O., et al. 2000. Preservation of mitochondrial structure and function after Bid- or Bax-mediated cytochrome c release. J. Cell Biol. 150:1027-1036.
33. Waterhouse, N.J., et al. 2001. Cytochrome c maintains mitochondrial transmembrane potential and ATP generation after outer mitochondrial membrane permeabilization during the apoptotic process. J. Cell Biol. 153:319-328.
34. Ricci, J.E., et al. 2004. Disruption of mitochondrial function during apoptosis is mediated by caspase cleavage of the p75 subunit of complex I of the electron transport chain. Cell. 117:773-786.
35. Ricci, J.E., Gottlieb, R.A., and Green, D.R. 2003. Caspase-mediated loss of mitochondrial function and generation of reactive oxygen species during apoptosis. J Cell Biol. 160:65-75.
36. Baines, C.P., et al. 2005. Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death. Nature. 434:658-662.
37. Nakagawa, T., et al. 2005. Cyclophilin D-dependent mitochondrial permeability transition regulates some necrotic but not apoptotic cell death. Nature. 434:652-658.
38. Green, D.R. 2005. Apoptotic pathways: ten minutes to dead. Cell. 121:671-674.
39. Halestrap, A. 2005. Biochemistry, a pore way to die. Nature. 434:578-579.
40. Adams, J.M., and Cory, S. 1998. The Bcl-2 protein family: arbiters of cell survival. Science. 281:1322-1326.
41. Scorrano, L., et al. 2003. BAX and BAK regulation of endoplasmic reticulum Ca2+: a control point for apoptosis. Science. 300:135-139.
42. Wei, M.C., et al. 2001. Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science. 292:727-730.
43. Lindsten, T., et al. 2000. The combined functions of proapoptotic Bcl-2 family members bak and bax are essential for normal development of multiple tissues. Mol. Cell. 6:1389-1399.
44. Knudson, C.M., Tung, K.S., Tourtellotte, W.G., Brown, G.A., and Korsmeyer, S.J. 1995. Bax-deficient mice with lymphoid hyperplasia and male germ cell death. Science. 270:96-99.
45. Nechushtan, A., Smith, C.L., Lamensdorf, I., Yoon, S.H., and Youle, R.J. 2001. Bax and Bak coalesce into novel mitochondria-associated clusters during apoptosis. J. Cell Biol. 153:1265-1276.
46. Eskes, R., Desagher, S., Antonsson, B., and Martinou, J.C. 2000. Bid induces the oligomerization and insertion of Bax into the outer mitochondrial membrane. Mol. Cell. Biol. 20:929-935.
47. Kuwana, T., et al. 2005. BH3 domains of BH3-only proteins differentially regulate Bax-mediated mitochondrial membrane permeabilization both directly and indirectly. Mol. Cell. 17:525-535.
48. Suzuki, M., Youle, R.J., and Tjandra, N. 2000. Structure of Bax: coregulation of dimer formation and intracellular localization. Cell. 103:645-654.
49. Liu, X., Dai, S., Zhu, Y., Marrack, P., and Kappler, J.W. 2003. The structure of a Bcl-xL/Bim fragment complex: implications for Bim function. Immunity. 19:341-352.
50. Desagher, S., et al. 1999. Bid-induced conformational change of Bax is responsible for mitochondrial cytochrome c release during apoptosis. J Cell Biol. 144:891-901.
51. Yethon, J.A., Epand, R.F., Leber, B., Epand, R.M., and Andrews, D.W. 2003. Interaction with a membrane surface triggers a reversible conformational change in Bax normally associated with induction of apoptosis. J. Biol. Chem. 278:48935-48941.
52. Chipuk, J.E., Maurer, U., Green, D.R., and Schuler, M. 2003. Pharmacologic activation of p53 elicits Bax-dependent apoptosis in the absence of transcription. Cancer Cell. 4:371-381.
53. Chipuk, J.E., et al. 2004. Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis. Science. 303:1010-1014.
54. Letai, A., et al. 2002. Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics. Cancer Cell. 2:183-192.
55. Cartron, P.P., et al. 2004. The first alpha helix of Bax plays a necessary role in its ligand-induced activation by the BH3-only proteins Bid and PUMA. Mol. Cell. 16:807-818.
56. Chen, L., et al. 2005. Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function. Mol. Cell. 17:393-403.
57. L, but not Bcl-2, until displaced by BH3-only proteins. Genes Dev. 19:1294-1305.
58. Tan, K.O., et al. 2001. MAP-1, a novel proapoptotic protein containing a BH3-like motif that associates with Bax through its Bcl-2 homology domains. J. Biol. Chem. 276:2802-2807.
59. Sawada, M., et al. 2003. Ku70 suppresses the apoptotic translocation of Bax to mitochondria. Nat. Cell Biol. 5:320-329.
60. Guo, B., et al. 2003. Humanin peptide suppresses apoptosis by interfering with Bax activation. Nature. 423:456-461.
61. Cohen, H.Y., et al. 2004. Acetylation of the C terminus of Ku70 by CBP and PCAF controls Bax-mediated apoptosis. Mol. Cell. 13:627-638.
62. Cuddeback, S.M., et al. 2001. Molecular cloning and characterization of Bif-1. A novel Src homology 3 domain-containing protein that associates with Bax. J. Biol. Chem. 276:20559-20565.
63. Cheng, E.H., Sheiko, T.V., Fisher, J.K., Craigen, W.J., and Korsmeyer, S.J. 2003. VDAC2 inhibits BAK activation and mitochondrial apoptosis. Science. 301:513-517.
64. Sawada, M., Hayes, P., and Matsuyama, S. 2003. Cytoprotective membrane-permeable peptides designed from the Bax-binding domain of Ku70. Nat. Cell Biol. 5:352-357.
65. Lum, J.J., et al. 2003. Vpr R77Q is associated with long-term nonprogressive HIV infection and impaired induction of apoptosis. J. Clin. Invest. 111:1547-1554. doi:10.1172/JCI200316233.
66. Poncet, D., et al. 2004. An anti-apoptotic viral protein that recruits Bax to mitochondria. J. Biol. Chem. 279:22605-22614.
67. Arnoult, D., et al. 2004. Cytomegalovirus cell death suppressor vMIA blocks Bax- but not Bak-mediated apoptosis by binding and sequestering Bax at mitochondria. Proc. Natl. Acad. Sci. U. S. A. 101:7988-7993.
68. Lindholm, D., Eriksson, O., and Korhonen, L. 2004. Mitochondrial proteins in neuronal degeneration. Biochem. Biophys. Res. Commun. 321:753-758.
69. Rao, K.V., and Norenberg, M.D. 2004. Manganese induces the mitochondrial permeability transition in cultured astrocytes. J. Biol. Chem. 279:32333-32338.
70. Lowell, B.B., and Shulman, G.I. 2005. Mitochondrial dysfunction and type 2 diabetes. Science. 307:384-387.
71. Reed, J.C. 1999. Dysregulation of apoptosis in cancer. J. Clin. Oncol. 17:2941-2953.
72. Tschopp, J., Martinon, F., and Hofmann, K. 1999. Apoptosis: silencing the death receptors [review]. Curr. Biol. 9:R381-R384.
73. Davis, S., Weiss, M.J., Wong, J.R., Lampidis, T.J., and Chen, L.B. 1985. Mitochondrial and plasma membrane potentials cause unusual accumulation and retention of rhodamine 123 by human breast adenocarcinoma-derived MCF-7 cells. J. Biol. Chem. 260:13844-13850.
74. Leprat, P., Ratinaud, M.H., and Julien, R. 1990. A new method for testing cell ageing using two mitochondria specific fluorescent probes. Mech. Ageing Dev. 52:149-167.
75. Modica-Napolitano, J.S., et al. 1996. Selective damage to carcinoma mitochondria by the rhodacyanine MKT-077. Cancer Res. 56:544-550.
76. Propper, D.J., et al. 1999. Phase I trial of the selective mitochondrial toxin MKT077 in chemo-resistant solid tumours. Ann. Oncol. 10:923-927.
77. Britten, C.D., et al. 2000. A phase I and pharmacokinetic study of the mitochondrial-specific rhodacyanine dye analog MKT 077. Clin. Cancer Res. 6:42-49.
78. Morgan, J., and Oseroff, A.R. 2001. Mitochondria-based photodynamic anti-cancer therapy. Adv. Drug Deliv. Rev. 49:71-86.
79. Belzacq, A.S., et al. 2001. Apoptosis induction by the photosensitizer verteporfin: identification of mitochondrial adenine nucleotide translocator as a critical target. Cancer Res. 61:1260-1264.
80. Brown, S.B., Brown, E.A., and Walker, I. 2004. The present and future role of photodynamic therapy in cancer treatment. Lancet Oncol. 5:497-508.
81. Zhang, T.D., et al. 2001. Arsenic trioxide, a therapeutic agent for APL. Oncogene. 20:7146-7153.
82. Grad, J.M., et al. 2001. Ascorbic acid enhances arsenic trioxide-induced cytotoxicity in multiple myeloma cells. Blood. 98:805-813.
83. Sordet, O., et al. 2001. Mitochondria-targeting drugs arsenic trioxide and lonidamine bypass the resistance of TPA-differentiated leukemic cells to apoptosis. Blood. 97:3931-3940.
84. Belzacq, A.S., et al. 2001. Adenine nucleotide translocator mediates the mitochondrial membrane permeabilization induced by lonidamine, arsenite and CD437. Oncogene. 20:7579-7587.
85. Di Cosimo, S., et al. 2003. Lonidamine: efficacy and safety in clinical trials for the treatment of solid tumors [review]. Drugs Today (Barc.). 39:157-174.
86. Oudard, S., et al. 2003. Phase II study of lonidamine and diazepam in the treatment of recurrent glioblastoma multiforme. J. Neurooncol. 63:81-86.
87. Don, A.S., et al. 2003. A peptide trivalent arsenical inhibits tumor angiogenesis by perturbing mitochondrial function in angiogenic endothelial cells. Cancer Cell. 3:497-509.
88. Pisha, E., et al. 1995. Discovery of betulinic acid as a selective inhibitor of human melanoma that functions by induction of apoptosis. Nat. Med. 1:1046-1051.
89. Fulda, S., Susin, S.A., Kroemer, G., and Debatin, K.M. 1998. Molecular ordering of apoptosis induced by anticancer drugs in neuroblastoma cells. Cancer Res. 58:4453-4460.
90. Fulda, S., and Debatin, K.M. 2000. Betulinic acid induces apoptosis through a direct effect on mitochondria in neuroectodermal tumors. Med. Pediatr. Oncol. 35:616-618.
91. Thurnher, D., et al. 2003. Betulinic acid: a new cytotoxic compound against malignant head and neck cancer cells. Head Neck. 25:732-740.
92. Fulda, S., Jeremias, I., and Debatin, K.M. 2004. Cooperation of betulinic acid and TRAIL to induce apoptosis in tumor cells. Oncogene. 23:7611-7620.
93. Hirsch, T., et al. 1998. PK11195, a ligand of the mitochondrial benzodiazepine receptor, facilitates the induction of apoptosis and reverses Bcl-2-mediated cytoprotection. Exp. Cell Res. 241:426-434.
94. Banker, D.E., et al. 2002. PK11195, a peripheral benzodiazepine receptor ligand, chemosensitizes acute myeloid leukemia cells to relevant therapeutic agents by more than one mechanism. Leuk. Res. 26:91-106.
95. Decaudin, D., et al. 2002. Peripheral benzodiazepine receptor ligands reverse apoptosis resistance of cancer cells in vitro and in vivo. Cancer Res. 62:1388-1393.
96. Marczin, N., El-Habashi, N., Hoare, G.S., Bundy, R.E., and Yacoub, M. 2003. Antioxidants in myocardial ischemia-reperfusion injury: therapeutic potential and basic mechanisms. Arch. Biochem. Biophys. 420:222-236.
97. Chen, Z., et al. 1998. Overexpression of MnSOD protects against myocardial ischemia/reperfusion injury in transgenic mice. J. Mol. Cell. Cardiol. 30:2281-2289.
98. Yoshimoto, T., Uchino, H., He, Q.P., Li, P.A., and Siesjo, B.K. 2001. Cyclosporin A, but not FK506, prevents the downregulation of phosphorylated Akt after transient focal ischemia in the rat. Brain Res. 899:148-158.
99. Matsumoto, S., Isshiki, A., Watanabe, Y., and Wieloch, T. 2002. Restricted clinical efficacy of cyclosporin A on rat transient middle cerebral artery occlusion. Life Sci. 72:591-600.
100. Waldmeier, P.C., Feldtrauer, J.J., Qian, T., and Lemasters, J.J. 2002. Inhibition of the mitochondrial permeability transition by the nonimmunosuppressive cyclosporin derivative NIM811. Mol. Pharmacol. 62:22-29.
101. Serkova, N.J., Christians, U., and Benet, L.Z. 2004. Biochemical mechanisms of cyclosporine neurotoxicity. Mol. Interv. 4:97-107.
102. Niemann, C.U., et al. 2002. Close association between the reduction in myocardial energy metabolism and infarct size: dose-response assessment of cyclosporine. J. Pharmacol. Exp. Ther. 302:1123-1128.
103. Jacotot, E., et al. 2001. Control of mitochondrial membrane permeabilization by adenine nucleotide translocator interacting with HIV-1 viral protein rR and Bcl-2. J. Exp. Med. 193:509-519.
104. Phenix, B.N., Lum, J.J., Nie, Z., Sanchez-Dardon, J., and Badley, A.D. 2001. Antiapoptotic mechanism of HIV protease inhibitors: preventing mitochondrial transmembrane potential loss. Blood. 98:1078-1085.
105. Wang, J.L., et al. 2000. Structure-based discovery of an organic compound that binds Bcl-2 protein and induces apoptosis of tumor cells. Proc. Natl. Acad. Sci. U. S. A. 97:7124-7129.
106. Tzung, S.P., et al. 2001. Antimycin A mimics a cell-death-inducing Bcl-2 homology domain 3. Nat. Cell Biol. 3:183-191.
107. Degterev, A., et al. 2001. Identification of small-molecule inhibitors of interaction between the BH3 domain and Bcl-xL. Nat. Cell Biol. 3:173-182.
108. Oltersdorf, T., et al. 2005. An inhibitor of Bcl-2 family proteins induces regression of solid tumors. Nature. 435:677-681.
109. Holinger, E.P., Chittenden, T., and Lutz, R.J. 1999. Bak BH3 peptides antagonize Bcl-xL function and induce apoptosis through cytochrome c-independent activation of caspases. J. Biol. Chem. 274:13298-13304.
110. Walensky, L.D., et al. 2004. Activation of apoptosis in vivo by a hydrocarbon-stapled BH3 helix. Science. 305:1466-1470.
111. Lin, B., et al. 2004. Conversion of Bcl-2 from protector to killer by interaction with nuclear orphan receptor Nur77/TR3. Cell. 116:527-540.
112. Rodi, D.J., et al. 1999. Screening of a library of phage-displayed peptides identifies human bcl-2 as a taxol-binding protein. J. Mol. Biol. 285:197-203.
113. Deverman, B.E., et al. 2002. Bcl-xL deamidation is a critical switch in the regulation of the response to DNA damage. Cell. 111:51-62.
114. Waters, J.S., et al. 2000. Phase 1 clinical and pharmacokinetic study of bcl-2 antisense oligonucleotide therapy in patients with non-Hodgkin's lymphoma. J. Clin. Oncol. 18:1812-1823.
115. Chi, K.N., et al. 2001. A phase I dose-finding study of combined treatment with an antisense Bcl-2 oligonucleotide (Genasense) and mitoxantrone in patients with metastatic hormone-refractory prostate cancer. Clin. Cancer Res. 7:3920-3927.
116. Egle, A., Harris, A.W., Bouillet, P., and Cory, S. 2004. Bim is a suppressor of Myc-induced mouse B cell leukemia. Proc. Natl. Acad. Sci. U. S. A. 101:6164-6169.
117. Letai, A., Sorcinelli, M.D., Beard, C., and Korsmeyer, S.J. 2004. Antiapoptotic BCL-2 is required for maintenance of a model leukemia. Cancer Cell 6:241-249.
118. Tan, T.-T., et al. 2005. Key roles of BIM-driven apoptosis in epithelial tumors and rational chemotherapy. Cancer Cell. 7:227-238.